Biologic and behavioral associations of estrogen receptor alpha positivity in head and neck squamous cell carcinoma

Virginia Drake, Elaine Bigelow, Carole Fakhry, Melina Windon, Lisa M. Rooper, Patrick Ha, Brett Miles, Christine Gourin, Rajarsi Mandal, Wojciech Mydlarz, Nyall London, Peter S. Vosler, Siddhartha Yavvari, Tanya Troy, Tim Waterboer, David W. Eisele, Gypsyamber D'Souza

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Objectives: Tumor HPV status is an established independent prognostic marker for oropharynx cancer (OPC). Recent studies have reported that tumor estrogen receptor alpha (ERα) positivity is also associated with prognosis independent of HPV. Little is known about the biologic and behavioral predictors of ERα positivity in head and neck squamous cell cancer (HNSCC). We therefore explored this in a multicenter prospective cohort study. Materials and Methods: Participants with HNSCC completed a survey and provided a blood sample. Tumor samples were tested for ERα using immunohistochemistry. ERα positivity was defined as ≥1%, standardized by the American Society of Clinical Oncology/College of American Pathologists in breast cancer. Characteristics were compared with χ2 and Fisher's exact test. Odds ratios (OR) were calculated using logistic regression. Results: Of 318 patients with HNSCC, one third had ERα positive tumors (36.2%, n = 115). Odds of ERα expression were significantly increased in those with HPV-positive tumors (OR = 27.5, 95% confidence interval[CI] 12.1–62), smaller tumors (≤T2, OR = 3.6, 95% CI 1.9–7.1), male sex (OR = 2.0, 95% CI 1.1–3.6), overweight/obesity (BMI ≥ 25, OR = 1.9, 95% CI 1.1–3.3), and those married/living with a partner (OR = 1.7, 95% CI 1.0–3.0). In a multivariate model, HPV-positivity (aOR = 27.5, 95% CI 11.4–66) and small tumor size (≤T2, aOR = 2.2, 95% CI 1.0–4.8) remained independently associated with ERα status. When restricted to OPC (n = 180), tumor HPV status (aOR = 17.1, 95% CI 2.1–137) and small tumor size (≤T2, aOR = 4.0 95% CI 1.4–11.3) remained independently associated with ERα expression. Conclusion: Tumor HPV status and small tumor size are independently associated with ERα expression in HNSCC.

Original languageEnglish
Article number105461
JournalOral Oncology
StatePublished - Oct 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Ltd


  • Estrogen receptor alpha
  • Head and neck neoplasms
  • Oropharyngeal neoplasms
  • Papillomaviridae
  • Tumor biomarkers

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research


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